Early stage trials demonstrate potential in hard-to-treat patients

Presenting data at the annual congress of the European Society for Medical Oncology (ESMO 20120) in Vienna, Austria, Ariad said that an ongoing phase I/II trial demonstrated “compelling clinical evidence of the anti-tumour activity of AP26113” in patients with non-small cell lung cancer (NSCLC) who test positive for a mutation in the anaplastic lymphoma kinase receptor.

There was also “initial clinical evidence” of anti-tumour activity in NSCLC patients with a mutation to the epidermal growth factor receptor (EGFR).

The trial has so far involved 29 patients with NSCLC, 14 who are ALK+ and 11 who have the EGFR mutation, with participants divided across six groups all taking a different dose of AP26113.

Each patient's condition was either unmanageable with current therapies, or there were no standard treatments available.

Across 11 patients with ALK+ who were among the cohorts receiving the five highest dose levels, anti-tumour activity was reported in eight. This included six of the nine who had demonstrated resistance to treatment with Pfizer's Xalkori (crizotinib), as well as both patients in this group who had not previously received Xalkori.

Results were less impressive for patients with the EGFR mutation who had previously failed on treatment with Roche/Astellas' Tarceva (erlotinib), although one patient in this group achieved some tumour shrinkage, while two had stable disease.

The company's president of R&D and chief scientific officer, Tim Clackson, told PMLiVE the drug's development would now move further with a phase II trial.

Clackson outlined the potential of the drug in patients for whom “there is no meaningful option for those who fail current treatment”, with around 250,000 NSCLC patients with the EGFR mutation across the world, half of whom will fail on existing therapies.

He also pointed to research showing the ALK mutation occurs in 4 per cent of NSCLC patients, or around 40,000 cases worldwide each year.

In addition, Clackson said Ariad plans to continue development of AP26113 without a more high profile partner, following a similar path to the development of its leukaemia drug ponatinib.

That medicine is now under review in both the Europe and the US, and Ariad's CEO Dr Harvey Berger has previously said peak year sales across multiple indications could top $1.5m if the drug is approved.